Diastolic left ventricular function in relation to circulating metabolic biomarkers in a population study

Area of Science:

• Cardiology
• Metabolomics
• Biochemistry

Background:

• Asymptomatic left ventricular diastolic dysfunction affects 25% of the population and is a significant risk factor for cardiovascular disease.
• Identifying modifiable biomarkers associated with diastolic dysfunction is crucial for early intervention and prevention strategies.

Purpose of the Study:

• To investigate the association between circulating metabolic biomarkers and asymptomatic left ventricular diastolic dysfunction.
• To explore the role of specific metabolites and metabolic pathways in maintaining diastolic left ventricular function.

Main Methods:

• Doppler echocardiography was used to assess early left ventricular relaxation (e') and left ventricular filling pressure (E/e') in 570 individuals.
• Serum metabolites were quantified using magnetic resonance spectroscopy, with 43 metabolites analyzed.
• Statistical analyses, including multivariable adjustments and partial least squares, were employed to determine correlations and associations over a five-year interval.

Main Results:

• Increased levels of the branched-chain amino acid valine and glucose+taurine were associated with improved e' (early left ventricular relaxation).
• Higher valine levels correlated with decreased E/e' (left ventricular filling pressure), indicating better diastolic function.
• Lower baseline levels of glucose+taurine were associated with a reduced risk of developing left ventricular diastolic dysfunction over follow-up.
• Consistent associations were observed for amino acids (2-aminobutyrate, 4-hydroxybutyrate, leucine, valine) with better diastolic function, and for glucose+glutamine and pentanoate with worse function.
• Branched-chain amino acid metabolism and aminoacyl-tRNA biosynthesis emerged as key metabolic pathways linked to left ventricular diastolic dysfunction.

Conclusions:

• Circulating amino acids, particularly branched-chain amino acids, show consistent associations with diastolic left ventricular function over time.
• Branched-chain amino acid metabolism and aminoacyl-tRNA biosynthesis are implicated as critical pathways in maintaining diastolic left ventricular function.
• These findings suggest potential therapeutic targets within these metabolic pathways for managing or preventing diastolic dysfunction.